Substituted tripyrranes have been recognized as important building blocks for synthesizing a wide variety of polypyrrolic macrocycles. See, for example, PCT Publication WO 97/32884 for a description of previously known tripyrranes, their methods of synthesis and use in preparing macrocyclic compounds. Previously known tripyrranes have in general been symmetrical. Symmetrical in this context means, for example, that in the tripyrrane compound represented by Formula A below:
R1 is the same as R6, R2 is the same as R5, and R3 is the same as R4, and accordingly there is a plane of symmetry between R3 and R4.
In those cases known in the art where the tripyrranes have been partially symmetric, the requirements of the prior art syntheses dictate that the dissymmetry arises solely at the center pyrrole, and not from the two outer pyrroles, which are the same as above. That is, R1 is the same as R6, and R2 is the same as R5, but R3 is no longer the same as R4. For partially symmetric tripyrranes of this nature, see Cavaleiro, J. A. C. S., et al., J.Chem.Soc., Perkin Trans 1, 21:2471–2478, 1973; Sessler, J. L., et al., Synlett, 2:187–188, 1996; Rocha Gonsalves, A. M. D'A., et al., Tetrahedron Lett., 22:2203–2206, 1972.
Non-symmetric tripyrranes—that is, those tripyrranes of Formula A in which R1 is not the same as R6 and/or R2 is not the same as R5, and R3 and R4 are the same or different—have not been previously disclosed, nor has a process for their synthesis. The ability to synthesize non-symmetric tripyrranes would provide a route for the preparation of novel polypyrrole macrocycles having desirable biodistribution or pharmacokinetic properties. A process for the synthesis of non-symmetric tripyrranes has now been discovered.